{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:36:29Z","timestamp":1793147789280,"version":"4.5.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"Introduction<\/jats:title>Aromatase excess syndrome (AEXS) is a rare, autosomal dominant disorder, characterized by enhanced aromatization of androgens and estrogen excess. In males it is characterized by pre-\/peripubertal gynecomastia, hypogonadotropic hypogonadism, advanced bone age and short adult height. Only a few female patients have been described so far.<\/jats:p><\/jats:sec>Methods<\/jats:title>We report on a family with four members with AEXS and present the long-term effects of aromatase inhibitor use in three of them. Genetic analysis showed a monoallelic 0.3-Mb deletion in 15q21, involving parts of CYP19A1<\/jats:italic>, GLDN<\/jats:italic> and DMXL2<\/jats:italic> in all four patients with AEXS.<\/jats:p><\/jats:sec>Results<\/jats:title>The index patient (male, 8 years old) presented with gynecomastia and accelerated growth and bone age. With start of puberty, estradiol levels increased, while testosterone levels remained low. Gynecomastia progressed and a mastectomy was performed twice. Presuming AEXS, a therapy with letrozole was initiated at the age of 19 years. Low-dose letrozole treatment was associated with an increase in testicular volume, increase in virilization and improvement in physical strength and libido. His brother (age 3 years) presented with accelerated growth and bone age. Treatment with letrozole, which was started at the age of 7 years, resulted in achieving an adult height of 179\u00a0cm and prevented the appearance of gynecomastia. His sister (age 6 years), who presented with premature thelarche and accelerated growth and bone age, was treated with an estrogen receptor modulator and a GnRH analog followed by letrozole treatment. Menarche occurred at age 13.5 years and adult height was 158\u00a0cm. Their father had an early, accelerated growth with an adult height of 171\u00a0cm, a delayed puberty and no gynecomastia. In vitro<\/jats:italic> studies provided evidence for involvement of aromatase induction in atypical cells and an increased range of potential mechanisms regulating aromatase activity due to the presence of the mutated allele.<\/jats:p><\/jats:sec>Discussion<\/jats:title>In conclusion, we observed a phenotypic variability within family members with AEXS carrying the same CYP19A1<\/jats:italic> microdeletion. When started early, treatment with letrozole was found to prevent the development of gynecomastia and increase adult height in one patient. In adult life, low-dose letrozole treatment resulted in improved physical strength and libido in the index patient.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2024.1487884","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T04:37:01Z","timestamp":1732077421000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Long term effects of aromatase inhibitor treatment in patients with aromatase excess syndrome"],"prefix":"10.3389","volume":"15","author":[{"given":"Eleni 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